Crystal structure of parallel quadruplexes from human telomeric DNA

@article{Parkinson2002CrystalSO,
  title={Crystal structure of parallel quadruplexes from human telomeric DNA},
  author={G. Parkinson and Michael P H Lee and S. Neidle},
  journal={Nature},
  year={2002},
  volume={417},
  pages={876-880}
}
Telomeric ends of chromosomes, which comprise noncoding repeat sequences of guanine-rich DNA, are fundamental in protecting the cell from recombination and degradation. Disruption of telomere maintenance leads to eventual cell death, which can be exploited for therapeutic intervention in cancer. Telomeric DNA sequences can form four-stranded (quadruplex) structures, which may be involved in the structure of telomere ends. Here we describe the crystal structure of a quadruplex formed from four… Expand
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It is proposed that these previously unobserved transient states represent the early and late intermediates toward the formation of stable G-quadruplexes, and may have mechanistic implications for the proteins and drugs that recognize G-rich sequences. Expand
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TLDR
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  • Journal of the American Chemical Society
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It is shown that four different G-quadruplex conformations are converted to a propeller-type parallel-stranded G- Quadruplex in K(+)-containing crowded solution due to water depletion, which reveals the formation of a new higher-order G- quadruplex structure under molecular crowding conditions. Expand
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TLDR
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TLDR
The energetic study shows that, a mixed hybrid type quadruplex conformation in which two parallel strands are bind with other two antiparallel strands, are more stable than other conformations. Expand
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TLDR
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Human telomeric sequence forms a hybrid-type intramolecular G-quadruplex structure with mixed parallel/antiparallel strands in potassium solution
TLDR
The folding structure of the human telomeric sequence in K+ solution determined by NMR demonstrates a novel, unprecedented intramolecular G-quadruplex folding topology with hybrid-type mixed parallel/antiparallel G-strands, and suggests a straightforward pathway for the secondary structure formation with effective packing within the extended human telomersic DNA. Expand
Structural basis for binding of porphyrin to human telomeres.
TLDR
The crystal structure of a bimolecular human telomeric quadruplex, of the sequence d(TAGGGTTAGGG), in a complex with the quadruplex-binding ligand 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin (TMPyP4) to a resolution of 2.09 A. Expand
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References

SHOWING 1-10 OF 32 REFERENCES
Quadruplex structure of Oxytricha telomeric DNA oligonucleotides
THE telomeres of most eukaryotes contain a repeating G-rich sequence with the consensus d(T/A)1–4G1–8, of which 12–16 bases form a 3' single-strand overhang beyond the telomeric duplex1. It has beenExpand
Solution structure of the human telomeric repeat d[AG3(T2AG3)3] G-tetraplex.
TLDR
The availability of the d[AG3(T2AG3)3] solution structure containing four AG3 human telomeric repeats should permit the rational design of ligands that recognize and bind with specificity and affinity to the individual grooves of the G-tetraplex, as well as to either end containing the diagonal and lateral loops. Expand
In vitro generated antibodies specific for telomeric guanine-quadruplex DNA react with Stylonychia lemnae macronuclei
TLDR
Experimental evidence is provided that the telomeres of Stylonychia macronuclei adopt in vivo a guanine-quadruplex structure, indicating that this structure may have an important role for telomere functioning. Expand
Structure and stability of human telomeric sequence.
TLDR
The overall structure and stability of telomeric sequences are modulated by the cation present, loop sequence, and the number of G tracts, which might be important for the telomere function. Expand
Accelerated assembly of G-quadruplex structures by a small molecule.
TLDR
Results imply that some biological effects elicited by G- quadruplex-interactive agents, such as the induction of anaphase bridges, may stem from the propensity such compounds have for assembling G-quadruplexes. Expand
G-Quadruplex DNA Structures Variations on a Theme
TLDR
The plethora of Gquadruplex DNA structures is explored, and their possible biological functions as well as the proteins that interact with them are discussed. Expand
DNA G-quartets in a 1.86 A resolution structure of an Oxytricha nova telomeric protein-DNA complex.
TLDR
The G-quartet:protein contact surfaces are modest and might simply represent crystal packing interactions, but it is interesting to speculate that the two types of telomeric DNA-protein interactions observed here might both be important in telomere biology. Expand
The crystal structure of a parallel-stranded guanine tetraplex at 0.95 A resolution.
TLDR
Evidence that the sugar conformation is strained is presented and it is proposed that this originates from forces that optimize guanine base stacking, which results from a simple crankshaft rotation that requires no net change in theugar conformation. Expand
NMR-Based model of a telomerase-inhibiting compound bound to G-quadruplex DNA.
TLDR
3,4,9, 10-perylenetetracarboxylic diimide-based ligands are identified as potent inhibitors of human telomerase by using a primer extension assay that does not use PCR-based amplification of the telomersase primer extension products. Expand
Ethidium derivatives bind to G-quartets, inhibit telomerase and act as fluorescent probes for quadruplexes.
TLDR
Ethidium derivatives that stabilize G-quadruplexes are described, which showed a potent anti-telomerase activity in vitro, and may be used to reveal the formation of multi-stranded DNA structures by standard fluorescence imaging, and therefore become fluorescent probes of quadruplex structures. Expand
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